Electron microscopic techniques will be employed to obtain more cogent information of plasma lipoprotein ultrastructure and metabolism. Further studies are projected on the interaction of individual C- apoproteins with lipids; specific information on protein-lipid complex formation with the neutral lipids, triglyceride and cholesteryl ester, will be sought. Complexes are to be isolated ultracentrifugally or by column chromatography and the various subfractions are to be examined in the electron microscope. The morphological studies will be carried out in conjunction with compositional studies on the isolated complexes. Investigations will also be carried out on abnormal lipoproteins found in Tangier disease. Ultracentrifugally and chromatographically isolated lipoprotein subfractions from both heterozygotic and hemozygotic individuals will be analyzed in the electron microscope and correlated with chemical and flotational information. In depth ultrastructural studies are to be undertaken on the pathogenesis of fatty livers generated by abnormal cholesterol metabolism in guinea pigs. We are particularly interested in localizing intracellular sites of cholesterol deposition in hepatocytes by applying autoradiographic techniques to ultrathin sections.